"Chemotherapy combined with surgical resection remains the standard of care," he said. "Treatment with immune checkpoint inhibitors or other immunotherapeutic agents should be considered in the context of clinical trials as we seek to improve cure rates for teens and young adults with this rare disease."

As reported in Nature Communications, Dr. Livingston and colleagues studied osteosarcoma specimens from 48 children and adults (median age at diagnosis, 27; 60% male; 63% white) with relapsed (23%) and metastatic (51%) disease.

They performed whole genome, RNA, and T-cell receptor sequencing, as well as immunohistochemistry and reverse phase protein array profiling.

Unlike other cancer types, the genomic changes seen in the osteosarcomas were not associated with an increase in the expression of mutated proteins (neoantigens), which are thought to stimulate an immune response against the tumor.

Gene expression analysis revealed "hot" tumors, which had high levels of immune infiltration, but also high levels of resistance pathways. "Cold" tumors had the lowest levels of immune infiltration, decreased expression of human leukocyte antigen, and a higher number of deleted genes, signaling higher genomic instability.

The findings lay the groundwork for clinical trials that combine immune checkpoint inhibitors with other agents, such as PARP inhibitors or cell-based therapies, to improve outcomes, according to Dr. Livingston. "We currently have two clinical trials based upon this study that are in development, with plans to open at MD Anderson Cancer Center within the next year," he said.

"The patient population is small because osteosarcoma is a rare disease," she said. "Several efforts are underway, such as the just announced OSProject, which will facilitate sample collection to address this numbers problem." (http://bit.ly/2Ibc4Ln)

That project and others should also facilitate follow-up studies to validate the prognostic factors identified in the current study, she said.